Figure 4.

Top: In human liver cancer stem cells, HOTAIR blocks the recruitment of transcription factor CREB, the coactivator P300, and RNA polymerase II to the SETD2 promoter region, resulting in repressed transcription of this important H3K36 methylator and thus impairing DNA damage response. Bottom: Platinum chemotherapy for ovarian cancer initiates the DDR, leading to activation of NF-κB, which induces HOTAIR. In the platinum-induced DDR reaction, HOTAIR also activates the NF-κB signaling cascade. This results in a positive feedback loop of sustained NF-κB activation and DNA-damage signaling, promoting cellular senescence and chemoresistance.